Experiments are proposed to investigate the hypothalamic control of gonadotropin secretion in the female rhesus monkey. The goals set for this proposal are 1) to test the hypothesis that the positive feedback effect of progesterone occurs at the level of the medial basal hypothalamus (MBH) to stimulate the release of luteinizing hormone releasing hormone (LHRH), 2) to study the electrical activity of neurons in the MBH in relation to the release of LHRH, and 3) to establish neurotransmitter mechanisms regulating the release of LHRH in primates. Progesterone administration following estrogen will be used as a primary stimulus for the release of gonadotropins and presumably LHRH. In the first series of experiments pituitary portal blood will be collected for measurements of LHRH, biogenic amines, and biogenic amine metabolites in order to determine the effects of progesterone on these parameters and to define possible involvement of neurotransmitters for the release of LH. In the second series of experiments complete deafferentations or lesions of the MBH will be made to determine the site of action of progesterone. In the third series of experiments extracellular recording will be made from antidromically identified neurons of the arcuate nucleus in order to study the electrical activity during the release of LHRH. In the fourth series of experiments the neurotransmitter mechanisms which control the release of LHRH from peptidergic neurons will be investigated by administering agonists and antagonists of bioamines, opioid substances and prostaglandins. In addition to experiments with drugs, measurements of neurotransmitters and their metabolites in CSF and perfusates of hypothalamus will be carried out. Results from the project will not only provide evidence to support the proposed hypothesis, but will also clarify the mechanisms by which the hypothalamus controls release of gonadotropins in subhuman primates.